Applications of Machine Learning in Histopathology: From Diagnostic Accuracy to Prognostic Insights

Main Article Content

Züleyha Doğanyiğit

Keywords

Artificial intelligence, Histopathology, Cancer diagnosis, Digital pathology, Personalized treatment

Abstract

Background: Histopathological examination remains the gold standard for evaluating morphological alterations in tissues and plays a pivotal role in both disease diagnosis and therapeutic decision-making. With the exponential growth of digital pathology, the integration of artificial intelligence (AI), particularly machine learning (ML) algorithms, has emerged as a transformative approach to optimize histopathological workflows. Objective: This review aims to systematically evaluate recent advances in ML applications within histopathology, focusing on their roles in enhancing diagnostic precision and enabling prognostic stratification across various malignancies. Methods: A comprehensive literature analysis was conducted, encompassing peer-reviewed studies that investigate the implementation of ML models in histopathological image interpretation, classification, segmentation, and outcome prediction. Emphasis was placed on convolutional neural networks, and ensemble learning techniques. Findings: Machine learning-based approaches demonstrate high sensitivity and specificity in the detection and classification of neoplastic lesions, particularly in breast, colorectal, thyroid, gastric, and head and neck cancers. These tools facilitate intraoperative consultation, mitotic figure quantification, and tumor grading, thereby improving diagnostic accuracy and reproducibility. Moreover, emerging prognostic models incorporating histopathological features show potential in predicting disease recurrence, overall survival, and treatment response, supporting the paradigm shift toward personalized medicine. Conclusions: The incorporation of ML into histopathological practice holds substantial potential to revolutionize diagnostic and prognostic processes. As algorithmic models continue to evolve and validate in clinical settings, their integration may redefine standard-of-care practices and bridge the gap between pathology and computational medicine.

Downloads

Download data is not yet available.

Abstract 0 | PDF Downloads 0

References

1.Maxwell, P., Salto-Tellez, M. Validation of immunocytochemistry as a morphomolecular technique. Cancer Cytopathol. 2016;124(8):540–545. https://doi.org/10.1002/cncy.21692.
2.Hamet, P., Tremblay, J. Artificial intelligence in medicine. Metab Clin Exp. 2017;69S:S36–S40. https://doi.org/10.1016/j.metabol.2017.01.011.
3.Bejnordi, B.E., Veta, M., Van Diest, P.J., et al. Diagnostic assessment of deep learning algorithms for detection of lymph node metastases in women with breast cancer. JAMA. 2017;318(22):2199–2210. https://doi.org/10.1001/jama.2017.14585.
4.Wang, H., Cruz-Roa, A., Basavanhally, A., et al. Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features. J Med Imaging. 2014;1(3):034003–034003. https://doi.org/10.1117/1.JMI.1.3.034003.
5.Sirinukunwattana, K., Pluim, J.P.W., Chen, H., et al. Gland segmentation in colon histology images: the glas challenge contest.  Med İmage Anal . 2017;35:489–502. https://doi.org/10.1016/j.media.2016.08.008.
6.Colling, R., Pitman, H., Oien, K., et al. Artificial intelligence in digital pathology: a roadmap to routine use in clinical practice. J Pathol. 2019;249(2):143–150. https://doi.org/10.1002/path.5310.
7.Hilgers, L., Ghaffari Laleh, N., West, N.P., et al. Automated curation of large-scale cancer histopathology image datasets using deep learning. Histopathology. 2024;84(7):1139–1153. https://doi.org/10.1111/his.15159.
8.McCorduck P., Cfe, C. Machines who think: a personal inquiry into the history and prospects of artificial intelligence, 2nd editioni. A.K. Peters/CRC Press: New York, USA; 2004. https://doi.org/10.1201/9780429258985.
9.Murphy, K.P. Machine Learning: A probabilistic perspective. MIT Press: Cambridge, England; 2012.
10.Fogel, A.L., Kvedar, J.C. Artificial intelligence powers digital medicine. NPJ Digital Med. 2018;1:5. https://doi.org/10.1038/s41746-017-0012-2.
11.Rajpurkar, P., Chen, E., Banerjee, O., et al. AI in health and medicine. Nature Med. 2022;28(1):31–38. https://doi.org/10.1038/s41591-021-01614-0.
12.Mondal, B. Artificial Intelligence: State of the Art. In Recent Trends and Advances in Artificial Intelligence and Internet of Things; Balas, V.E., Kumar, R., eds. Springer: Cham, Switzerland; 2020. https://doi.org/10.1007/978-3-030-32644-9_32.
13.Wulczyn, E., Steiner, D.F., Xu, Z., et al. Deep learning-based survival prediction for multiple cancer types using histopathology images. PloS One. 2020;15(6):e0233678. https://doi.org/10.1371/journal.pone.0233678.
14.Cao, Y., Yang, Y., Chen, Y., et al. Optimizing thyroid AUS nodules malignancy prediction: a comprehensive study of logistic regression and machine learning models. Front Endocrinol. 2024;15:1366687. https://doi.org/10.3389/fendo.2024.1366687.
15.Nohman, A.I., Ivren, M., Alhalabi, O.T., et al. Intraoperative label-free tissue diagnostics using a stimulated Raman histology imaging system with artificial intelligence: an initial experience. Clin Neurol Neurosurg. 2024;247:108646. https://doi.org/10.1016/j.clineuro.2024.108646.
16.Bakoglu, N., Cesmecioglu, E., Sakamoto, H., et al. Artificial intelligence-based automated determination in breast and colon cancer and distinction between atypical and typical mitosis using a cloud-based platform. Pathol Oncol Res (POR). 2024;30:1611815. https://doi.org/10.3389/pore.2024.1611815.
17.Yoshida, H., Shimazu, T., Kiyuna, T., et al. Automated histological classification of whole-slide images of gastric biopsy specimens. Gastric Cancer. 2018;21(2):249–257. https://doi.org/10.1007/s10120-017-0731-8.
18.Wibawa, M.S., Zhou, J.Y., Wang, R., et al. AI-based risk score from tumour-infiltrating lymphocyte predicts locoregional-free survival in nasopharyngeal carcinoma. Cancers. 2023;15(24):5789. https://doi.org/10.3390/cancers15245789.
19.Schmidl, B., Hütten, T., Pigorsch, S., et al. Assessing the role of advanced artificial intelligence as a tool in multidisciplinary tumor board decision-making for recurrent/metastatic head and neck cancer cases – the first study on ChatGPT 4o and a comparison to ChatGPT 4.0. Front Oncol. 2024;14:1455413. https://doi.org/10.3389/fonc.2024.1455413.
20.Mahmood, H., Shaban, M., Indave, B.I., et al. Use of artificial intelligence in diagnosis of head and neck precancerous and cancerous lesions: a systematic review. Oral Oncol. 2020;110:104885. https://doi.org/10.1016/j.oraloncology.2020.104885.
21.Lan, J., Chen, M., Wang, J., et al. Using less annotation workload to establish a pathological auxiliary diagnosis system for gastric cancer. Cell Rep Med. 2023;4(4):101004. https://doi.org/10.1016/j.xcrm.2023.101004.
22.Iizuka, O., Kanavati, F., Kato, K., et al. Deep learning models for histopathological classification of gastric and colonic epithelial tumours. Sci Rep. 2020;10(1):1504. https://doi.org/10.1038/s41598-020-58467-9.
23.Jeyaraj, P.R., Samuel Nadar, E.R. Computer-assisted medical image classification for early diagnosis of oral cancer employing deep learning algorithm. J Cancer Res Clin Oncol. 2019;145(4):829–837. https://doi.org/10.1007/s00432-018-02834-7.
24.Ferber, D., Wölflein, G., Wiest, I.C., et al. In-context learning enables multimodal large language models to classify cancer pathology images. Nature Comm. 2024;15(1):10104. https://doi.org/10.1038/s41467-024-51465-9.
25.Koyama, J., Morise, M., Furukawa, T., et al. Artificial intelligence-based personalized survival prediction using clinical and radiomics features in patients with advanced non-small cell lung cancer. BMC Cancer. 2024;24(1):1417. https://doi.org/10.1186/s12885-024-13190-w.
26.Xia, L., Xu, T., Zheng, Y., et al. Lymph node metastasis prediction from in situ lung squamous cell carcinoma histopathology images using deep learning. Lab İnvest. 2025;105(1):102187. https://doi.org/10.1016/j.labinv.2024.102187.
27.Wang, X., Janowczyk, A., Zhou, Y., et al. Prediction of recurrence in early stage non-small cell lung cancer using computer extracted nuclear features from digital H&E images. Sci Rep. 2017;7(1):13543.
https://doi.org/10.1038/s41598-017-13773-7.
28.Tsou, P., Wu, C.J. Mapping driver mutations to histopathological subtypes in papillary thyroid carcinoma: applying a deep convolutional neural network. J Clin Med. 2019;8(10):1675. https://doi.org/10.3390/jcm8101675.
29.Coudray, N., Ocampo, P.S., Sakellaropoulos, T., et al. Classification and mutation prediction from non–small cell lung cancer histopathology images using deep learning. Nature Med. 2018;24(10):1559–1567. https://doi.org/10.1038/s41591-018-0177-5.
30.Nirschl, J.J., Janowczyk, A., Peyster, E.G., et al. A deep-learning classifier identifies patients with clinical heart failure using whole-slide images of H&E tissue. PloS One. 2018;13(4):e0192726. https://doi.org/10.1371/journal.pone.0192726.
31.Wei, J.W., Wei, J.W., Jackson, C.R., et al. Automated detection of celiac disease on duodenal biopsy slides: a deep learning approach. J Pathol İnform. 2019;10:7. https://doi.org/10.4103/jpi.jpi_87_18.
32.LeCun, Y., Bengio, Y., Hinton, G. Deep learning. Nature, 2015;521(7553):436–444. https://doi.org/10.1038/nature14539.
33.Bahadir, C.D., Omar, M., Rosenthal, J. et al. Artificial intelligence applications in histopathology.  Nat Rev Electr Eng . 2024;1:93–108. https://doi.org/10.1038/s44287-023-00012-7.
34.Jarrett, D., Stride, E., Vallis, K., et al. Applications and limitations of machine learning in radiation oncology. Br J Radiol. 2019;92(1100):20190001. https://doi.org/10.1259/bjr.20190001.
35.Qaiser, T., Lee, C.Y., Vandenberghe, M., et al. Usability of deep learning and H&E images predict disease outcome-emerging tool to optimize clinical trials. NPJ Prec Oncol. 2022;6(1):37. https://doi.org/10.1038/s41698-022-00275-7.
36.Lapuente-Santana, Ó., Kant, J., Eduati, F. Integrating histopathology and transcriptomics for spatial tumor microenvironment profiling in a melanoma case study. NPJ Prec Oncol. 2024;8(1):254. https://doi.org/10.1038/s41698-024-00749-w.
37.Wang, J.M., Hong, R., Demicco, E.G., et al. Deep learning integrates histopathology and proteogenomics at a pan-cancer level. Cell Rep Med. 2023;4(9):101173. https://doi.org/10.1016/j.xcrm.2023.101173.
38.Adeoye, J., Tan, J.Y., Choi, S.W., et al. Prediction models applying machine learning to oral cavity cancer outcomes: a systematic review. Int J Med İnform. 2021;154:104557. https://doi.org/10.1016/j.ijmedinf.2021.104557.
39.Ding, W., Abdel-Basset, M., Hawash, H., et al. Explainability of artificial intelligence methods, applications and challenges: a comprehensive survey. Inform Sci. 2022;615(C):238–292. https://doi.org/10.1016/j.ins.2022.10.013.
40.Provenzano, E., Driskell, O.J., O'Connor, D.J., et al. The important role of the histopathologist in clinical trials: challenges and approaches to tackle them. Histopathology. 2020;76(7):942–949. https://doi.org/10.1111/his.14099.
41.McAlpine, E.D., Michelow, P. The cytopathologist's role in developing and evaluating artificial intelligence in cytopathology practice. Cytopathology. 2020;31(5):385–392. https://doi.org/10.1111/cyt.12799.
42.Hays, P. Artificial intelligence in cytopathological applications for cancer: a review of accuracy and analytic validity. Eur J Med Res. 2024;29(1):553. https://doi.org/10.1186/s40001-024-02138-2.
43.Mobadersany, P., Yousefi, S., Amgad, M., et al. Predicting cancer outcomes from histology and genomics using convolutional networks. Proc Nat Acad Sci. 2018;115(13):E2970–E2979. https://doi.org/10.1073/pnas.1717139115.
44.Hao, J., Kosaraju, S.C., Tsaku, N.Z., et al. PAGE-Net: interpretable and integrative deep learning for survival analysis using histopathological images and genomic data. In Pacific symposium on biocomputing 2020, Proceedings of the Pacific Symposium, Hawaii, USA, 3–7 January 2020; Altman, R.B, Dunker, A.K, eds. World Scientific Publishing Company: Singapore, 2019; pp. 355–366. https://doi.org/10.1142/9789811215636_0032.
45.Amer, F., Hammoud, S., Khatatbeh, H., et al. How to engage health care workers in the evaluation of hospitals: development and validation of BSC-HCW1—a cross-sectional study. Int J Environ Res Public Health. 2022;19(15):9096. https://doi.org/10.3390/ijerph19159096.
46.Khafaji, M.A., Safhi, M.A., Albadawi, R.H., et al. Artificial intelligence in radiology: are Saudi residents ready, prepared, and knowledgeable? Saudi Med J. 2022;43(1):53–60. https://doi.org/10.15537/smj.2022.43.1.20210337.
47.Farhud, D.D., Zokaei, S. Ethical issues of artificial intelligence in medicine and healthcare. Iran J Public Health, 2021;50(11):i–v. https://doi.org/10.18502/ijph.v50i11.7600.
48.Park, S.H., Choi, J., Byeon, J.S. Key principles of clinical validation, device approval, and insurance coverage decisions of artificial intelligence. Korean J Radiol. 2021;22(3):442–453. https://doi.org/10.3348/kjr.2021.0048.